rs3002430

Variant names:

• chr6-165876668-G-A
• rs3002430
• ENST00000647768.3:c.106+109440C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-165876668-G-A
• chr6-165876668-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000647768.3(PDE10A):​c.106+109440C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 152,118 control chromosomes in the GnomAD database, including 45,263 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.77 (45263 hom., cov: 32)
• Consequence: PDE10A ENST00000647768.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810
• Publications: 4 publications found

Genes affected

PDE10A (HGNC:8772): (phosphodiesterase 10A) The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase family. It plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This protein can hydrolyze both cAMP and cGMP to the corresponding nucleoside 5' monophosphate, but has higher affinity for cAMP, and is more efficient with cAMP as substrate. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Dec 2011]

PDE10A Gene-Disease associations (from GenCC):

• striatal degeneration, autosomal dominant 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• dyskinesia, limb and orofacial, infantile-onset

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics
• infantile-onset generalized dyskinesia with orofacial involvement

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• childhood-onset benign chorea with striatal involvement

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE10A	XM_011535387.4	c.58+34140C>T		intron_variant	Intron 2 of 23		XP_011533689.2
PDE10A	XM_017010194.3	c.58+34140C>T		intron_variant	Intron 2 of 23		XP_016865683.1
PDE10A	XM_017010197.3	c.58+34140C>T		intron_variant	Intron 2 of 18		XP_016865686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE10A	ENST00000647768.3	c.106+109440C>T		intron_variant	Intron 1 of 22			ENSP00000497930.3
PDE10A	ENST00000672902.1	c.-18+110861C>T		intron_variant	Intron 1 of 22			ENSP00000500351.1
PDE10A	ENST00000672859.1	c.-308-84333C>T		intron_variant	Intron 1 of 24			ENSP00000500900.1

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116954 AN: 152000 Hom.: 45221 Cov.: 32

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.862

Gnomad AMR AF: 0.798

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.960

Gnomad SAS AF: 0.878

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.771

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.769 AC: 117049 AN: 152118 Hom.: 45263 Cov.: 32 AF XY: 0.777 AC XY: 57755 AN XY: 74348

African (AFR) AF: 0.754 AC: 31254 AN: 41474

American (AMR) AF: 0.798 AC: 12195 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 2542 AN: 3470

East Asian (EAS) AF: 0.960 AC: 4976 AN: 5184

South Asian (SAS) AF: 0.877 AC: 4229 AN: 4820

European-Finnish (FIN) AF: 0.803 AC: 8504 AN: 10584

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.746 AC: 50714 AN: 67992

Other (OTH) AF: 0.774 AC: 1633 AN: 2110

Alfa AF: 0.756 Hom.: 15637

Bravo AF: 0.769

Asia WGS AF: 0.921 AC: 3201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.26
DANN	Benign	0.63
PhyloP100		-0.081

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3002430; hg19: chr6-166290156;